Melanocytic tumors with spitzoid morphology: correlation of clinicopathologic features and FISH analysis.

BACKGROUND: A subset of melanocytic tumors with spitzoid morphology may lead to potential inaccurate diagnosis and lack of assessment of malignancy potential. In this study, we aimed to evaluate melanocytic tumors with spitzoid morphology using conventional melanoma FISH (RREB-1, CCND1, MYB and CEP6) and 9p21 FISH (CDKN2A) probes and compare the probe results with clinical and histopathological features. METHODS: This study is a multicentric retrospective study including three centers, Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Department of Pathology, Acibadem University, School of Medicine, Department of Pathology and ETA Pathology Laboratory. The pathology reports in archives of these three centers between 2015 and 2017 have been reviewed for cases diagnosed as atypical Spitz tumor or melanoma with Spitzoid features. These cases were selected for the study. We analyzed 39 cases of atypical Spitz tumor (AST), 10 cases of melanomas with spitzoid features for clinicopathological data and chromosomal alterations, targeting RREB-1 (6p25), CCND1 (11q13), MYB (6q23), together with 9p21 (CDKN2A), using FISH methodology. RESULTS: Thirty out of total 49 cases showed chromosomal alterations by 4-probe melanoma FISH assay, 22 (56.4%) cases were ASTs, and 8 (80%) cases were melanomas. Eighteen out of 49 cases showed homozygote deletion by 9p21 FISH assay, 12 (30.8%) cases were ASTs, and 6 (60%) cases were melanomas. When histopathological data were compared with FISH results, a statistically significant correlation was found between 9p21 FISH positivity (homozygous deletion) and presence of deep mitosis (p < 0.05). In addition, epidermal consumption (p = 0.07) and increased mitotic activity (p = 0.05) were more frequent in cases with homozygous 9p21 deletion, but these differences did not reach statistical significance. When the clinical features were considered, there was a statistically significant correlation between 9p21 FISH positivity and the diameter (p < 0.05). There was no statistically significant correlation between melanoma FISH assay and any of the histopathological or clinical data. DISCUSSION: These data suggest that 9p21 FISH positivity correlated with more worrisome histopathologic and clinical features, such as deep mitosis, increased mitotic activity, epidermal consumption, and larger lesion size, so these features are precious, pointing out spitzoid lesions with higher risk. However, there is a need for further studies using FISH or similar techniques in order to provide more accurate prognostic information in lesions Blank morphology.

Cutaneous rhabdomyosarcoma with FUS::TFCP2 fusion: A case report emphasizing early detection.

Rhabdomyosarcoma with TFCP2 rearrangement is a recently identified malignant neoplasm characterized by immunohistochemical evidence of rhabdomyoblastic differentiation, keratin expression, upregulation of ALK, and an aggressive clinical course. This neoplasm has a tendency to affect craniofacial bones, with only a few reported cases of extra-osseous tumors. Here, we present a case of cutaneous rhabdomyosarcoma with FUS::TFCP2 fusion in a 35-year-old female. Notably, the tumor exhibited a pathologic spectrum, initially resembling sclerosing dermatitis at presentation but progressing into a high-grade malignant tumor within 8 months. The distinctive immunoprofile of this neoplasm highlights the importance of early molecular studies for diagnosis, even in the presence of low-grade cytomorphology. Early detection may offer an opportunity for timely resection before the tumor becomes unresectable.

Dermatofibroma with Verocay Body-Type Palisading Features and a Brief Discussion on Potential Schwannoma Mimickers of the Skin.

Several types of cutaneous tumors can show palisading features or the so-called rippled pattern. The list includes adnexal tumors such as trichoblastoma and sebaceoma, basal cell carcinoma, leiomyoma, perineuroma, myofibroblastoma, and even malignant melanoma. Dermatofibroma, which is known for having a large variety of histological patterns, is also in the list. Here we present a case of dermatofibroma with palisading features strikingly similar to Verocay bodies of schwannoma.

Multiple Military Osteoma Cutis: Report of a Case and a Brief Review of the Literature.

A 39-year-old woman presented with a 4-year history of asymptomatic facial lesions that has progressively increased in number to become a cosmetic nuisance. These lesions have not responded to 6-months of topical 20% azelaic acid, 0.1% retinoic acid, and 20% vitamin C combination. She has had mild papulopustular acne. Her personal and family histories were unremarkable. On dermatologic examination, there were multiple flesh-colored to pigmented, firm ovoid to round papules, 2-5 mm in size, over the forehead and both cheeks (Figure 1). The dermatoscopic examination was nonspecific. Preliminary diagnoses were made of eccrine syringoma, steatocystoma multiplex, and papular elastorrhexis. A histopathologic examination from a punch biopsy displayed focal ossification within the dermis (Figure 2). Routine laboratory tests, including serum calcium, phosphorus, PTH, and vitamin D levels were within the normal ranges. A maxillofacial 3D CT scan, revealed multiple dermal and hypodermal ossifications, <3-5 mm in size-in the frontal, mandibular, and maxillary areas of the face (Figure 3). Scattered osteomas were also seen on the neck. A definitive diagnosis of multiple miliary osteoma cutis (MMOC) of the face and neck was firmly established based on clinical, histologic, and radiologic findings. Radiologically, the distribution and extent of the lesions were more pronounced than clinically anticipated. (SKINmed. 2022;20:469-471).

A Review on Cutaneous and Musculoskeletal Manifestations of CLOVES Syndrome.

CLOVES syndrome is a novel sporadic mosaic segmental overgrowth syndrome, currently categorized under the canopy of PROS (PIK3CA-related overgrowth spectrum) disorders. All PROS disorders harbor heterozygous postzygotic activating somatic mutations involving the PIK3CA gene. As an upstream regulator of the PI3K/AKT/mTOR signal transduction pathway, activating mutations of PIK3CA gene commence in uncontrolled growth of cutaneous, vascular (capillaries, veins, and lymphatics), adipose, neural, and musculoskeletal tissues. The excessive growth is segmental, patchy, asymmetric, and confined to body parts affected by the mutation. The term 'CLOVES' is an acronym denoting congenital lipomatous overgrowth, vascular malformations, epidermal nevi and spinal (scoliosis) and/ or skeletal anomalies. The syndrome is characterized by an admixture of overgrown tissues, derived mainly from mesoderm and neuroectoderm. Among PROS disorders, CLOVES syndrome represents the extreme end of the spectrum with massive affection of almost the entire body. The syndrome might judiciously be treated with medications hampering with the PI3K/AKT/mTOR signal transduction pathway. This article aims at reviewing the cutaneous and musculoskeletal manifestations of CLOVES syndrome, as the paradigm for PROS disorders. CLOVES syndrome and other PROS disorders are still misdiagnosed, underdiagnosed, underreported, and undertreated by the dermatology community.

Analysis of interobserver reproducibility in grading dysplastic nevi: Results of the application of the 2018 World Health Organization grading criteria.

BACKGROUND: We aimed to determine whether the histopathological grading of dysplastic nevi is an objective endeavor, considering interobserver variability, according to 2018 World Health Organization (WHO) criteria. METHODS: In total, 179 cases of dysplastic nevi, with high and moderate degree of atypia, diagnosed and graded according to the previous criteria were reviewed by three pathologists. Then, the observers graded the dysplastic nevi as low or high according to 2018 WHO criteria. RESULTS: Grading of dysplastic nevi was in complete agreement in 99 out of 179 cases across three observers with a fair level of overall interobserver agreement (multirater κfree : 0.40). The observers showed moderate to good agreement for most of the architectural features, except for criteria regarding focal continuous basal proliferation of melanocytes, density of non-nested junctional melanocytes, and presence of dyscohesive nests of intraepidermal melanocytes, whereas fair agreement was achieved for the cytological criteria. CONCLUSIONS: The 2018 WHO criteria for dysplastic nevus will ensure a common approach to the diagnosis and grading of dysplastic nevi. However, histopathological criteria, such as cytological features and focal continuous basal proliferation of melanocytes, should be improved so as to ensure a more accurate surgical approach and risk assessment.

Livedoid cutaneous metastasis of signet-ring cell gastric carcinoma.

Cutaneous metastasis of gastric cancer is extremely rare. Nodular forms are more common and inflammatory forms are exceptionally encountered. Herein, we report a case of inflammatory cutaneous metastasis of signet-ring cell gastric cancer (poorly cohesive gastric carcinoma with signet-ring cell component) masquerading as livedo reticularis. To our knowledge, such a clinical presentation of cutaneous metastasis has not been reported for gastric cancer. It is imperative to preserve a high index of clinical suspicion for diagnosing cutaneous metastases. Our case highlights the importance of obtaining a skin biopsy in patients with a known history of internal malignancy. Bizarre, newly erupting, evolving, persistent, or treatment-refractory dermatologic lesions (such as nodules, ulcers, erythematous, reticular, or livedoid patches) might be clues for an underlying internal malignancy and require prompt histopathological sampling. Personal medical history, histopathological examination, and immunohistochemical profiling are equally important in distinguishing primary cutaneous carcinomas from secondary metastatic deposits. Early recognition of a cutaneous metastasis might enable appropriate staging and timely intervention, thereby prolonging survival.

Proliferating Pilar Tumors: Can Immunohistochemistry Differentiate Benign and Malignant Forms?

BACKGROUND: Proliferating pilar tumor (PPT) is an adnexal tumor of purported differentiation toward the follicular outer root sheath. Immunohistochemistry has been suggested to differentiate between benign and malignant forms. METHODS: Eleven benign (PPT) and 9 malignant PPT lesions were reviewed; Ki67, p27, and p53 were applied. The staining intensity (strong, moderate, weak, and negative), positive cell numbers, and marker indexes (%) were scored using image-analysis software (ViraSoft). RESULTS: Overall, there was no significant correlation between Ki67 and p53 and histopathological features. However, malignant PPTs had significantly lower numbers of p27-positive cells (P = 0.030). CONCLUSIONS: Our study includes the largest group of patients in whom image analysis of p53, Ki67, and p27 has been used to try to separate benign from malignant lesions. Although there were no significant differences regarding Ki67 and p53, malignant lesions have a statistically lower expression of p27. Further studies may be needed to determine the clinical usefulness of image analysis in this differential diagnosis.